JP6953866B2 - Hydrogel structure, its manufacturing method, and its use - Google Patents

Description

The present invention relates to a hydrogel structure, a method for producing the same, an active energy ray-curable liquid composition, and uses.

Vascular treatment mainly includes treatment of aneurysms (aneurysms), bypassing, cutting, and anastomosis of blood vessels.
These vascular treatments are often performed by intubating a catheter, which is a wire-shaped instrument, into the blood vessel. Regarding the catheter intubation, it is necessary to perform a procedure training, and the procedure training is performed using an animal other than a human when the human body is not used, or by using a blood vessel model.

However, when animals other than humans are used, blood vessels exist in the body, so catheter intubation is performed by irradiating the affected area with X-rays to visualize the blood vessels. Therefore, when the procedure training is repeatedly performed, there is a problem that the X-ray exposure dose of the operator increases.
Therefore, a catheter treatment simulator formed of a transparent material has been proposed (see, for example, Patent Document 1).

It is also used for a blood vessel model that imitates a patient's blood vessel (see, for example, Patent Document 2), a vascular lesion model formed from a plurality of small lesions having different hardness (for example, see Patent Document 3), and a preoperative simulation. A method for producing a blood vessel model (see, for example, Patent Document 4) has been proposed.

Further, for practice of procedures such as surgery, an organ model manufactured of silicone, urethane elastomer, styrene elastomer or the like is used. Surgeons and assistant staff are required to improve the procedure level to a certain level or higher in order to improve the quality of life (QOL) and the quality of life (QOL) of patients after surgery. Therefore, it is required to provide an organ model in which the tactile sensation, the internal structure, and the usability of surgical devices such as ultrasonic scalpels and electric scalpels are more similar to those of human organs.

Further, in recent years, the organ model composed of hydrogel has a problem that even if a blood vessel is arranged, there is no exudation of pseudo blood that imitates blood when the blood vessel is incised, and the surgical training lacks the sense of reality. Therefore, in order to give a sense of presence in the surgical training model, it is required that pseudo blood is produced when a blood vessel in the organ model is cut.
Therefore, as an organ model for the purpose of reproducing the texture of a human organ, a molding material for an organ model mainly composed of polyvinyl alcohol has been proposed (see, for example, Patent Document 5).
Further, an organ model using a material that liquefies by the heat of the heat generating device and elutes pseudo blood when cut by a heat generating device such as an electric knife has been proposed (see, for example, Patent Document 6).

An object of the present invention is to provide a hydrogel structure having a hollow tube structure having excellent transparency, useful as a blood vessel model, etc., and having a good usability of a surgical device such as an electric knife.

The hydrogel structure of the present invention as a means for solving the above-mentioned problems has a hollow tube structure having an inner diameter of 1.0 mm or less and a transmittance of 80% or more in the visible light region.

According to the present invention, it is possible to provide a hydrogel structure having a hollow tube structure having excellent transparency, useful as a blood vessel model, etc., and having a good usability of a surgical device such as an electric knife.

FIG. 1 is a schematic view showing an example of a blood vessel model (hydrogel structure) of the present invention. FIG. 2A is a schematic view showing an example of the blood vessel model (hydrogel structure) of the present invention. FIG. 2B is a schematic view showing another example of the blood vessel model (hydrogel structure) of the present invention. FIG. 3A is a schematic top view showing an example of a hydrogel structure to which a transparent hard body is attached. FIG. 3B is a schematic side view showing an example of a hydrogel structure to which a transparent hard body is attached. FIG. 4 is a schematic view showing an example of a modeled body manufacturing process using a three-dimensional modeling apparatus used in the method for manufacturing a hydrogel structure of the present invention. FIG. 5 is a schematic view showing an example (additive manufacturing method) of a three-dimensional modeling apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet ejection method. FIG. 7 is a schematic view showing an organ model in which the outer shape imitates the shape of an organ (liver) as one form of the hydrogel structure of the present invention.

(Hydrogel structure, blood vessel model, and organ model)
The hydrogel structure of the present invention has a hollow tube structure having an inner diameter of 1.0 mm or less and a transmittance of 80% or more in the visible light region. The hydrogel structure preferably further contains a mineral and a polymer, and is preferably composed of a hydrogel in which water is contained in a three-dimensional network structure formed by combining the polymer and the mineral. .. The hydrogel means a gel containing water as a main component.
The hydrogel structure of the present invention has a problem that the conventional catheter treatment simulator cannot be applied to a 3D print that can reproduce a complicated shape and a shape according to personal patient data because the manufacturing method is limited depending on the material used. , The produced blood vessel model has the disadvantage that it can only be placed on a two-dimensional plane and cannot reproduce the actual three-dimensional structure, and cannot be applied to preoperative simulation for treating the affected part of the three-dimensional structure. It is based on the finding that there is a problem.
Further, the hydrogel structure of the present invention is produced by three-dimensionally modeling a flexible material such as silicone rubber in the conventional blood vessel model, but it is an opaque model and the texture is similar to that of an actual blood vessel. Is based on the finding that there is a problem that is different.
Further, the hydrogel structure of the present invention has a problem that, in the conventional vascular lesion model, a plurality of materials are required to form a plurality of small lesions having different hardness. In addition, it is based on the finding that it is difficult to reproduce a detailed structure because it is modeled by a mold, and it is difficult to model based on patient personal data.
Furthermore, the hydrogel structure of the present invention can form a somewhat complicated shape by the conventional method for manufacturing a blood vessel model, but the transmittance of the blood vessel model is not high, and the texture is similar to that of an actual blood vessel. Is based on the finding that there is a problem that is different.
Further, the hydrogel structure of the present invention is based on the finding that the conventional organ model has a problem that the tactile sensation, the internal structure, and the usability are different from those of a real human organ.

The blood vessel model of the present invention comprises the hydrogel structure of the present invention.
The organ model of the present invention is composed of the hydrogel structure of the present invention, and its outer shape imitates the shape of an organ.

The hydrogel structure, blood vessel model, and organ model of the present invention can be suitably used for catheter intubation procedure training or preoperative simulation.

The hydrogel structure may have a hollow tube structure having an inner diameter of 1.0 mm or less, and the hydrogel structure itself has a hollow tube structure and a hollow having an inner diameter of 1.0 mm or less. It preferably has a tubular structure. For example, in the case of a blood vessel model, a dendritic hollow tube structure in which a blood vessel having an inner diameter of 1.0 mm or less and a blood vessel having an inner diameter of more than 1.0 mm are continuously and branched to be connected is a blood vessel closer to the actual human body. It is possible to reproduce the net.

The hydrogel structure of the present invention has a hollow tube structure having an inner diameter of 1.0 mm or less, preferably 0.5 mm or less, and more preferably 0.3 mm or less. The inner diameter can be measured by a method of measuring mechanically like a caliper, a method of measuring using a microscope or the like, or a method of measuring with a one-shot 3D shape measuring device (for example, manufactured by KEYENCE CORPORATION). be.
It is also possible to use something like a catheter with a known outer diameter to insert it inside the hollow tube structure and measure the inner diameter.
In the hydrogel structure of the present invention, the tip portion of the hollow tube may be thinned, the intermediate portion may be thinned, and one end opening may be thinner than the other end opening. Further, it may be branched or dendritic, and a vascular shape as shown in FIG. 1 is preferable.
The structure may be in communication, may have a closed portion in a part of the pipe, or may have a closed end. Further, the hollow pipe may be a double pipe or may be laminated.

Examples of the hollow duct structure include blood vessels, lymphatic vessels, esophagus, nasal cavity, external auditory canal, pharynx, larynx, oral cavity, trachea, bronchi, fine bronchi, stomach, small intestine (for example, duodenum, jejunum, ileum, etc.), and large intestine (for example, duodenum, jejunum, ileum, etc.). For example, the shape of the cecum, large intestine, rectum, anal canal, etc.), pancreatic duct, cystic duct, esophagus, bile duct, etc. can be used for various preoperative simulations, procedure exercises, and the like.

The hydrogel structure having the vascular structure can be suitably used as a vascular model.
The blood vessel model is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include those that reproduce arteries, veins, capillaries and the like.
FIG. 1 is a schematic view showing an example of a blood vessel model (hydrogel structure) of the present invention. As shown in FIG. 1, it has a blood vessel wall portion 51 and a blood vessel cavity portion 50. By adjusting the thickness of the blood vessel wall, the texture at the time of catheter insertion can be changed. For example, by increasing the thickness of the blood vessel membrane, it is possible to reproduce the texture of, for example, a blood vessel that has been hardened due to a disease or the like.
As the hydrogel structure, in order to allow a liquid imitating blood to flow into the blood vessel model, a liquid inflow port may be provided and a liquid circulation device may be attached.

FIG. 2A is a schematic view showing an example of the hydrogel structure of the present invention. As shown in FIG. 2A, the handleability and storage stability are improved by forming a structure in which the blood vessel model 52 having the blood vessel cavity portion 50 and the blood vessel wall portion 51 made of hydrogel is covered with another structure 53. Can be done. The other structure 53 may be a hydrogel, and in that case, the other structure 53 may also have a structure that also serves as a blood vessel wall portion 51 (in the other structure 53 that is a hydrogel). Hydrogel structure containing the cavity 50).

FIG. 2B is a schematic view showing another example of the hydrogel structure of the present invention. As shown in FIG. 2B, in a blood vessel model having a blood vessel cavity 50 and a blood vessel wall 51 composed of a first hydrogel body, a site such as a hump 55 having a low elastic coefficient as compared with a normal normal blood vessel. Can also be reproduced in a second hydrogel body having an elastic coefficient different from that of the first hydrogel to reproduce a vascular lesion model.
It is also possible to prepare a blood vessel model having a blood vessel wall portion composed of at least a first hydrogel body and a second hydrogel body, thereby reproducing the texture of a blood vessel hardened due to a disease or the like.

Further, the other structure 53 may have an outer shape imitating an organ, and can be suitably used as an organ model.

The organ model is not particularly limited and can be appropriately selected according to the purpose, and any internal organ part in the human body can be reproduced. For example, the brain, heart, bladder, as shown in FIG. Liver, kidney, pancreas, spleen, gallbladder, uterus, etc.

The transmittance of the hydrogel structure in the visible light region is 80% or more, preferably 85% or more, more preferably 90% or more, and particularly preferably 95% or more. When the transmittance is 80% or more, the inside of the hydrogel structure can be visualized. The transmittance can be measured using, for example, a spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, using an integration unit) or the like. The visible light region means a wavelength region having a wavelength of 400 nm or more and 700 nm or less.
As a method for measuring the transmittance, a hydrogel structure is cut in the longitudinal direction to form a flat sample. At this time, in order to prevent diffused reflection due to the influence of the unevenness of the sample surface, the measurement is performed with the integrating sphere unit used. Further, when measuring the details, it is also possible to measure using an optical fiber or the like. The flat plate shape means that the flat portion of the sample can be irradiated with the irradiation light, and the shape of the sample may be curved or flat.

The arithmetic mean surface roughness of the inner wall of at least a part of the hollow tube structure of the hydrogel structure is not particularly limited, but is 50 μm or less from the viewpoint of visibility from the outside and reproducibility of the inner wall of blood vessels and the like. Is preferable. In addition, the slipperiness of the catheter when the catheter is inserted into the blood vessel can be reproduced. In addition, the inner wall of an organ such as the large intestine can be reproduced, and the arithmetic mean surface roughness can be adjusted so that the endoscope does not get caught in the inner wall when the endoscope is inserted. The arithmetic mean surface roughness is preferably 40 μm or less, more preferably 30 μm or less, and particularly preferably 20 μm or less. The lower limit of the arithmetic mean surface roughness is not particularly limited, but is preferably 0.1 μm or more from the viewpoint of reproducibility of the inner wall texture of blood vessels and organs.
The arithmetic mean surface roughness shall be the surface roughness in an area of 500 μm square. The arithmetic mean surface roughness can be measured using, for example, a laser microscope (device name: VK-X100, manufactured by KEYENCE CORPORATION). This arithmetic mean surface roughness is preferably uniform over the entire inner wall of the hollow tube.

The coefficient of static friction of the inner wall of at least a part of the hollow tube structure of the hydrogel structure is preferably 0.1 or less, more preferably 0.05 or less. When the coefficient of static friction is 0.1 or less, a hydrogel structure can be produced that is closer to the texture of a living body and has a texture closer to that of an actual blood vessel or the like when a medical device such as a catheter is inserted. The lower limit of the coefficient of static friction is not particularly limited, but is preferably 0.01 or more, and more preferably 0.02 or more.
The coefficient of static friction is measured from the cut surface by cutting the hydrogel structure in the central portion of the hollow tube in the longitudinal direction. For example, using a ball-on-plate method using a surface measuring device (device name: TYPE: 38, manufactured by Shinto Kagaku Co., Ltd.), the probe can be dropped onto the blood vessel equivalent and the coefficient of static friction can be measured by point contact. can. The coefficient of static friction is preferably uniform over the entire inner wall of the hollow pipe.

The coefficient of static friction of at least a part of the inner wall of the hollow tube shape of the hydrogel structure is inside the hydrogel structure, for example, a solvent, oil, a surfactant that can be used as a lubricant for wet wire drawing, or the like. Can be adjusted by applying. These may be applied to the inner wall of the hydrogel structure or may be flowed into the tube in the form of a liquid.

The solvent is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include water and organic solvents. These may be used alone or in combination of two or more. Among these, an organic solvent is preferable from the viewpoint of preventing absorption by the hydrogel structure, and a high boiling point solvent is preferable from the viewpoint of preventing drying.

The oil is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include mineral oil, synthetic oil such as silicone, vegetable oil, wax and animal oil.

The surfactant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant and the like can be used. Can be mentioned. These may be used alone or in combination of two or more. Among these, a nonionic surfactant is preferable because it is not easily affected by the electrolyte in the hydrogel structure.

The nonionic surfactant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene alkyl phosphate, poly. Examples thereof include oxyethylene fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, fatty acid monoglyceride, sucrose fatty acid ester, and higher fatty acid alkanolamide.

The anionic surfactant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, alkyl sulfate, alkyl sulfate ether, alkyl amide ether sulfate, alkyl aryl polyether sulfate, monoglyceride sulfate, alkyl sulfonic acid can be selected. Acid, alkylamide sulfonic acid, alkylarylsulfonic acid, olefin sulfonic acid, paraffin sulfonic acid, alkylsulfosuccinic acid, alkylether sulfosuccinic acid, alkylamide sulfosuccinic acid, alkylsuccinamide acid, alkylsulfoacetate, alkyl phosphate, alkylphosphate, Examples thereof include metal salts such as acyl sulfonic acid, acyl acetylate, and acyl-N-acyl taurine, ammonium salts, amine salts, amino alcohol salts, magnesium salts, and basic amino acid salts.

The cationic surfactant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, chloride. Examples thereof include cetyltrimethylammonium, myristyldimethylbenzylammonium chloride, lanolin acetate fatty acid aminopropylethyldimethylammonium, dicocoyldimethylammonium chloride, lauryltrimethylammonium chloride, and ethylsulfate branched fatty acid aminopropylethyldimethylammonium.

The amphoteric tenside is not particularly limited and may be appropriately selected depending on the intended purpose. For example, an amide amino acid amphoteric tenside having an alkyl group, an alkenyl group or an acyl group having 8 to 24 carbon atoms. 2, Secondary amide type or tertiary amide type imidazoline type amphoteric tenside, carbobetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type having an alkyl group having 8 or more and 24 or less carbon atoms, an alkenyl group or an acyl group. Examples thereof include an amidosulfobetaine amphoteric tenside agent. Specifically, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, stearyldihydroxyethyl betaine, lauryl hydroxysulfobetaine, bis (stearyl-N-hydroxyethyl imidazoline) chloroacetate complex, lauryl dimethylamino. Examples thereof include betaine acetate, cocoylamide propyl betaine, and cocoyl alkyl betaine.

The hydrogel structure preferably satisfies at least one of the following (1) to (2).
(1) At least a part of the hollow tube shape is in contact with a hydrogel (second hydrogel body) having an elastic coefficient different from that of the hydrogel (first hydrogel body) constituting the hollow tube shape (1). 2) The hollow tube shape is formed by at least two types of hydrogels having different elastic ratios.

The elastic modulus of the hydrogel structure (first hydrogel body) at 20% compression is preferably 0.1 MPa or more and 1 MPa or less, and more preferably 0.2 MPa or more and 0.8 MPa or less. The elastic modulus is measured by using a universal testing machine (manufactured by Shimadzu Corporation, AG-I) and a compression jig for load cells 1 kN and 1 kN, and hydro containing a columnar metal having a diameter of 1 mm as a main component of water. The stress on the compression applied to the load cell by pushing it into the gel structure can be recorded on a computer, the stress on the amount of displacement can be plotted, and the elastic modulus can be measured. The elastic modulus can be controlled by adjusting the water content of the hydrogel structure.

Hydrogel body (first hydrogel body) 52 having the hollow tube structure and hydrogel body (second hydrogel body) having different elasticity as shown in FIGS. 2A and 2B. In the case of the gel structure, the elasticity of the second hydrogel body 53 in FIG. 2A and the aneurysm (second hydrogel body) 55 in FIG. 2B at 20% compression is 0.005 MPa or more and 0.1 MPa or less. Is preferable, and 0.01 MPa or more and 0.05 MPa or less is more preferable. The compression strength at the time of 70% compression is preferably 0.3 MPa or more and 1 MPa or less, and more preferably 0.4 MPa or more and 0.7 MPa or less.

When the elastic modulus of one part of the hydrogel structure is X (MPa) and the elastic modulus of the other part adjacent to the one part is Y (MPa), the absolute value of the change in elastic modulus (| X). -Y |) is 0.1 MPa or more, preferably 0.11 MPa or more. When the absolute value (| XY |) of the elastic modulus change is 0.1 MPa or more, the elastic modulus is different in the same hydrogel structure, so that the elastic modulus is different from that of a normal blood vessel such as an aneurysm in a blood vessel. It is possible to realize the texture of a vascular lesion model as shown in FIG. 2B, which has a site having a low elastic modulus.

As for the water content of the hydrogel structure having the hollow tube structure, the water content of the hydrogel (second hydrogel body) having an elastic coefficient different from that of the hydrogel structure (first hydrogel body). By lowering the elasticity, the elasticity of the hydrogel structure can be made higher than that of the hydrogel having an elasticity different from that of the hydrogel structure, and the reproducibility of the texture of the actual blood vessel is more excellent.
The water content of the hydrogel structure having a hollow tube shape (first hydrogel body) is not particularly limited and may be appropriately selected depending on the intended purpose, but is 30% by mass or more and 75% by mass or less. Is preferable.
The water content (second hydrogel body) of the hydrogel having an elastic modulus different from that of the hydrogel structure is not particularly limited and may be appropriately selected depending on the intended purpose, but is 50% by mass or more and 90. It is preferably mass% or less.
The water content can be measured using, for example, a heat-drying moisture meter (device name: MS-70, manufactured by A & D Co., Ltd.) or the like.

If necessary, the hydrogel structure is further mixed with water, a polymer, a mineral, an organic solvent, and other components by an appropriate method, inked as a hydrogel precursor, and the ink is cured by an appropriate method. You can get it.

<Polymer>
The polymer is not particularly limited and may be appropriately selected depending on the intended purpose, but a water-soluble polymer is preferable because the hydrogel contains water as a main component. By containing the water-soluble polymer, the strength of the hydrogel containing water as a main component can be maintained.
The water-soluble property of the water-soluble polymer means that, for example, when 1 g of the water-soluble polymer is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more of the water-soluble polymer is dissolved.

Examples of the polymer include polymers having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group and the like.

The polymer may be a homopolymer (homopolymer), a heteropolymer (copolymer), may be unmodified, or may have a known functional group introduced therein. It may be in the form of a salt. Of these, homopolymers are preferred.

The polymer can be obtained by polymerizing a polymerizable monomer. The polymerizable monomer will be described later in the method for producing a hydrogel structure.

The water-soluble polymer is obtained by polymerizing a polymerizable monomer, and examples of the polymerizable monomer include acrylamide, N-substituted acrylamide derivative, N, N-di-substituted acrylamide derivative, and N-substituted methacrylamide derivative. Examples thereof include N, N-di-substituted methacrylamide derivatives. These may be used alone or in combination of two or more.

By polymerizing the polymerizable monomer, a water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group and the like can be obtained. The water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group and the like is an advantageous constituent component for maintaining the strength of an aqueous gel.

The content of the polymer is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 0.5% by mass or more and 20% by mass or less with respect to the total amount of the hydrogel structure.

<Minerals>
The mineral is not particularly limited and may be appropriately selected depending on the intended purpose. However, since hydrogel contains water as a main component, a layered clay mineral that can be uniformly dispersed at the level of primary crystals in water is available. Preferably, water-swellable layered clay minerals are more preferred.

The water-swellable layered clay mineral presents a state in which two-dimensional disk-shaped crystals having a unit cell in the crystal are stacked, and when the water-swellable layered clay mineral is dispersed in water, each single-layer state is exhibited. Separated with to form a disk-shaped crystal.

The water-swellable clay mineral is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include water-swellable smectite and water-swellable mica. These may be used alone or in combination of two or more. Among these, water-swellable hectorite containing sodium as an interlayer ion, water-swellable montmorillonite, water-swellable saponite, and water-swellable synthetic mica are preferable, and water-swellable hectorite is suitable because a highly elastic bolus can be obtained. More preferred. The water swelling property means that water molecules are inserted between layers of layered clay minerals and dispersed in water.
The mineral may be an appropriately synthesized mineral or a commercially available product.

The commercially available product is not particularly limited and may be appropriately selected depending on the intended purpose. For example, synthetic hectorite (Raponite XLG, manufactured by RockWood), SWN (Coop Chemical Ltd.), fluorinated hectorite. SWF (manufactured by Coop Chemical Ltd.) and the like can be mentioned. These may be used alone or in combination of two or more.

The content of the mineral is not particularly limited and may be appropriately selected depending on the intended purpose. However, from the viewpoint of elastic modulus and hardness of the hydrogel structure, 1% by mass with respect to the total amount of the hydrogel structure. More than 40% by mass is preferable, and 1% by mass or more and 25% by mass or less is more preferable.

<Organic solvent>
In the present invention, an organic solvent can be added in order to enhance the moisturizing property of the hydrogel structure.
Examples of the organic solvent include a water-soluble organic solvent and the like. The water solubility of the water-soluble organic solvent means that the organic solvent can be dissolved in water in an amount of 30% by mass or more.

The water-soluble organic solvent is not particularly limited and may be appropriately selected depending on the intended purpose. For example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol, etc. Alkyl alcohols with 1 to 4 carbon atoms such as tert-butyl alcohol; amides such as dimethylformamide and dimethylacetamide; ketones or ketone alcohols such as acetone, methylethylketone and diacetone alcohol; ethers such as tetrahydrofuran and dioxane; Ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1,2,6-hexanetriol, thio Polyhydric alcohols such as glycols, hexylene glycols and glycerins; polyalkylene glycols such as polyethylene glycols and polypropylene glycols; ethylene glycol monomethyl (or ethyl) ethers, diethylene glycol methyl (or ethyl) ethers, triethylene glycol monomethyls (or ethyls) Lower alcohol ethers of polyhydric alcohols such as ethers; alkanolamines such as monoethanolamine, diethanolamine, triethanolamine; N-methyl-2-pyrrolidone, 2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone And so on. These may be used alone or in combination of two or more. Among these, polyhydric alcohol, glycerin and propylene glycol are preferable, and glycerin and propylene glycol are more preferable from the viewpoint of moisturizing property.

The content of the organic solvent is preferably 10% by mass or more and 50% by mass or less with respect to the total amount of the hydrogel structure. When the content is 10% by mass or more, the effect of preventing drying can be sufficiently obtained. Further, when it is 50% by mass or less, the mineral is uniformly dispersed.

<Water>
As the water, for example, ion-exchanged water, ultra-filtered water, reverse osmosis water, pure water such as distilled water, ultrapure water, or the like can be used.
Other components such as an organic solvent may be dissolved or dispersed in the water depending on the purpose of imparting moisturizing property, antibacterial property, conductivity, hardness adjustment and the like.

The water content is preferably 10% by mass or more and 99% by mass or less, more preferably 50% by mass or more and 98% by mass or less, and particularly preferably 60% by mass or more and 97% by mass or less, based on the total amount of the hydrogel structure. preferable.

<Other ingredients>
The other components are not particularly limited and may be appropriately selected depending on the intended purpose. For example, a stabilizer, a surface treatment agent, a polymerization initiator, a colorant, a viscosity modifier, an adhesive-imparting agent, and oxidation. Examples thereof include inhibitor, anti-aging agent, cross-linking accelerator, ultraviolet absorber, plasticizer, preservative, dispersant, and surfactant.

The surface of the hydrogel structure of the present invention is preferably covered with a transparent hard body.
FIG. 3A is a schematic top view showing an example of the hydrogel structure 60 to which the transparent hard body 61 is attached. FIG. 3B is a schematic side view showing an example of the hydrogel structure 60 to which the transparent hard body 61 is attached. As shown in FIGS. 3A and 3B, the surface is covered with a transparent hard body 61, which further maintains the shape of the blood vessel model and improves the handleability at the time of treatment and the storage stability of the blood vessel model (). It is possible to improve the drought resistance and antiseptic property, that is, to reduce the water vapor permeability and oxygen permeability of the hard body), and to improve the appearance of the blood vessel model.

The material for forming the hard body is not particularly limited and may be appropriately selected depending on the intended purpose. For example, a highly transparent plastic material such as an acrylic resin or a polycarbonate resin, or a highly transparent inorganic material such as glass. And so on.
The shape and average thickness of the hard body are not particularly limited and may be appropriately selected depending on the intended purpose.
The water vapor transmission rate ^{is preferably 500 g / m 2} · d or less. The water vapor transmission rate can be measured based on JIS K7129, for example, with a water vapor transmission rate meter (device name: Lyssy L80, manufactured by SYSYTECH) or the like.
The oxygen permeability is preferably 100,000 cc / m ² / hr / atm or less. The oxygen permeability can be measured based on JIS Z1702, for example, with a differential pressure type gas permeability meter (device name: Lyssy L100, manufactured by SYSYTECH) or the like.

(Procedure practice tool)
The procedure training tool of the present invention has at least one selected from a hydrogel structure, a blood vessel model, a structure, and an organ model, and at least one of a catheter and an endoscope, and further, if necessary. It has other members.

The catheter is not particularly limited and may be appropriately selected depending on the intended purpose. For example, angiography catheter, balloon catheter, cerebrovascular catheter, cancer catheter treatment, indwelling vascular catheter, indwelling suction catheter, urinary tract catheter. And so on.

The endoscope is not particularly limited and may be appropriately selected depending on the intended purpose. For example, a laryngeal endoscope, a bronchoscope, an upper gastrointestinal endoscope, a duodenal endoscope, a small intestinal endoscope, and a large intestine. Examples include endoscopy, thoracoscope, cystoscope, biliary tract, and angioscope.

The hydrogel structure, blood vessel model, and organ model of the present invention can be used for catheter intubation procedure training and preoperative simulation.
The catheter intubation procedure training referred to here is to train the procedure for intubating a catheter into a blood vessel model and reaching a target location. At this time, training is also included in which the thickness of the catheter is changed according to the purpose, a stent, a wire, a balloon or the like is provided at the tip, and this is treated or installed at an assumed site of the affected area.
Selecting the most suitable catheter according to the shape of the blood vessel is also a part of the training, and it is useful to handle one or more catheters and the hydrogel structure of the present invention as a set.

For such training, it is preferable to resemble the actual condition in the blood vessel. The blood vessel model or structure of the present invention is composed of hydrogel, and its texture is very similar to that of a living body, which makes it a useful material. It is also useful to provide a mechanism for flowing a liquid in the hydrogel structure and to train in a state where blood flow is generated.
Conventionally, since there are few transparent blood vessel models, it is also a useful point of the present invention that training that has been performed by irradiating and visualizing X-rays can be performed without the risk of X-ray exposure. ..

(Manufacturing method of hydrogel structure)
The first aspect of the method for producing a hydrogel structure of the present invention is not particularly limited, but for example, a columnar core portion (a support forming material, an active energy ray-curable liquid composition) is used. It can be manufactured by forming a support) and forming a tubular portion so as to cover the columnar core portion with a hydrogel forming material, and then removing the columnar core portion. At this time, it is preferable to use a layered manufacturing method such as a conventionally known material jet method (a method of forming a three-dimensional object by laminating by repeating a layer forming step and a layer curing step). The coating may be such that at least a part of the columnar core portion is covered with the hydrogel-forming material, and it is preferable that the coating is entirely covered. Further, it is preferable that both the core forming material (support forming material) and the hydrogel forming material are active energy ray-curable compositions. The number of repetitions varies depending on the size, shape, structure, etc. of the hydrogel structure to be produced and cannot be unconditionally specified, but if the average thickness per layer is in the range of 10 μm or more and 50 μm or less. It is possible to model with high accuracy and without peeling.

The second aspect of the method for producing a hydrogel structure of the present invention is a method for producing a hydrogel structure having a hollow tube structure, wherein a columnar core portion is formed by using a core portion forming material, and the above-mentioned A step of coating a columnar core portion with a hydrogel forming material to form a tubular portion is included, and the core portion forming material is an active energy ray-curable composition, and the active energy ray-curable composition. It is a material in which the cured product is liquefied by heat, and further includes other steps as necessary.
The second aspect of the method for producing a hydrogel structure does not include a step (removal step) for removing the columnar core portion in the first aspect of the method for producing a hydrogel structure.

Hereinafter, an example of a method for producing a hydrogel structure by the above-mentioned material jet method will be described in detail.

<< Layer forming process and layer forming means >>
The layer forming step is a step of discharging a hydrogel forming material containing water and a polymerizable monomer and a support forming material to be removed later to form a layer made of these materials.
The support forming material is applied at a position different from that of the hydrogel forming material, and after curing, becomes a support for supporting the hydrogel constituent portion. In the present invention, since the hollow tube structure is formed, the hollow upper portion thereof is in a state of being supported by the support at the time of stacking. The "position different from the hydrogel-forming material" means that the position where the support-forming material is applied and the position where the hydrogel-forming material is applied do not overlap, and the position where the support-forming material is applied and the position where the support-forming material is applied. , The position where the hydrogel forming material is applied may be adjacent to each other.

The method of applying the forming material as the layer forming step is not particularly limited as long as the droplets can be applied to a target place with appropriate accuracy, and can be appropriately selected depending on the purpose, for example. , Dispenser method, spray method, inkjet method and the like. A known device can be preferably used to carry out these methods.

Among these, the dispenser method is excellent in quantification of droplets, but the coating area is narrow, and the spray method can easily form fine ejected substances, has a wide coating area, and is excellent in coating property. The quantification of droplets is poor, and scattering occurs due to the spray flow. Therefore, in the present invention, the inkjet method is particularly preferable. The inkjet method has an advantage that the quantification of droplets is better than that of the spray method and a large coating area can be obtained as compared with the dispenser method, and is preferable in that a complicated three-dimensional shape can be formed accurately and efficiently. ..

In the case of the inkjet method, the nozzle has a nozzle capable of ejecting the forming material. As the nozzle, a nozzle in a known inkjet printer can be preferably used.

-Hydrogel forming material (hydrogel precursor)-
The hydrogel-forming material contains water and a polymerizable monomer, preferably contains a mineral and an organic solvent, and further contains a polymerization initiator and other components, if necessary.
As the water, the mineral, the organic solvent, and the other components, the same ones as those of the hydrogel structure can be used.

--Polymerizable monomer ---
The polymerizable monomer is a compound having one or more unsaturated carbon-carbon bonds, and a polymerizable monomer that is polymerized by active energy rays such as ultraviolet rays and electron beams is preferable.
Examples of the polymerizable monomer include a monofunctional monomer and a polyfunctional monomer. These may be used alone or in combination of two or more.
Examples of the polyfunctional monomer include a bifunctional monomer, a trifunctional monomer, a tetrafunctional or higher functional monomer, and the like.

The monofunctional monomer is a compound having one unsaturated carbon-carbon bond, and is, for example, acrylamide, an N-substituted acrylamide derivative, an N, N-di-substituted acrylamide derivative, an N-substituted methacrylamide derivative, N, N. -Di-substituted methacrylamide derivatives, other monofunctional monomers and the like. These may be used alone or in combination of two or more.

Examples of the N-substituted acrylamide derivative, N, N-di-substituted acrylamide derivative, N-substituted methacrylamide derivative, or N, N-di-substituted methacrylamide derivative include N, N-dimethylacrylamide (DMAA) and N-. Examples include isopropylacrylamide.

Examples of the other monofunctional monomer include 2-ethylhexyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, acryloylmorpholin (ACMO), and caprolactone-modified tetrahydrofurfuryl (meth). ) Acrylate, isobornyl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, lauryl (meth) acrylate, 2-phenoxyethyl (meth) acrylate, isodecyl (meth) acrylate, isooctyl (meth) ) Acrylate, tridecyl (meth) acrylate, caprolactone (meth) acrylate, ethoxylated nonylphenol (meth) acrylate, urethane (meth) acrylate and the like can be mentioned. These may be used alone or in combination of two or more.

By polymerizing the monofunctional monomer, a water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group and the like can be obtained.

The water-soluble polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group and the like is an advantageous constituent component for maintaining the strength of the vascular model.

Examples of the bifunctional monomer include tripropylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, and neopentyl glycol hydroxypivalic acid. Esterdi (meth) acrylate, neopentyl glycol hydroxypivalate di (meth) acrylate, 1,3-butanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (Meta) acrylate, 1,9-nonanediol di (meth) acrylate, diethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, tripropylene glycol di (meth) acrylate, caprolactone-modified neopentyl glycol of hydroxypivalate Estel di (meth) acrylate, propoxylated neopentyl glycol di (meth) acrylate, ethoxy-modified bisphenol A di (meth) acrylate, polyethylene glycol 200 di (meth) acrylate, polyethylene glycol 400 di (meth) acrylate, methylene bisacrylamide, etc. Can be mentioned. These may be used alone or in combination of two or more.

Examples of the trifunctional monomer include trimethylolpropane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, triallyl isocyanate, tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate, and ethoxylated trimethylolpropane. Examples thereof include tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, and propoxylated glyceryl tri (meth) acrylate. These may be used alone or in combination of two or more.

Examples of the tetrafunctional or higher functional monomer include pentaerythritol tetra (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, and penta (pentaerythritol tetra (meth) acrylate). Examples thereof include meta) acrylate ester and dipentaerythritol hexa (meth) acrylate. These may be used alone or in combination of two or more.

The content of the monofunctional monomer is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 1% by mass or more and 10% by mass or less with respect to the total amount of the hydrogel-forming material. More preferably 5% by mass or less. When the content is 1% by mass or more and 10% by mass or less, there is an advantage that the dispersion stability of minerals in the hydrogel-forming material is maintained and the stretchability of the hydrogel structure is improved. The stretchability refers to a property that stretches when the hydrogel structure is pulled and does not break.

The content of the polyfunctional monomer is preferably 0.001% by mass or more and 1% by mass or less, and more preferably 0.01% by mass or more and 0.5% by mass or less, based on the total amount of the hydrogel-forming material. When the content is 0.001% by mass or more and 1% by mass or less, the elastic modulus and hardness of the obtained hydrogel structure can be adjusted within an appropriate range.

The content of the polymerizable monomer is preferably 0.5% by mass or more and 20% by mass or less with respect to the total amount of the hydrogel-forming material. When the content is 0.5% by mass or more and 20% by mass or less, the strength of the hydrogel structure can be made closer to that of human organs.

--Polymerization initiator ---
The polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a photopolymerization initiator and a thermal polymerization initiator.
As the photopolymerization initiator, any substance that generates radicals by irradiation with light (particularly ultraviolet rays having a wavelength of 220 nm to 400 nm) can be used.

The photopolymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. For example, acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p. , P'-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, Michler ketone, benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, Benzylmethyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2-methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) -2-hydroxy-2-methylpropan-1-one, methyl Examples thereof include benzoylformate, 1-hydroxycyclohexylphenylketone, azobisisobutyronitrile, benzoylperoxide, di-tert-butylperoxide and the like. These may be used alone or in combination of two or more.

The thermal polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. For example, an azo-based initiator, a peroxide initiator, a persulfate initiator, a redox (oxidation-reduction) initiator. And so on. These may be used alone or in combination of two or more. Of these, peroxide initiators are preferred.

The peroxide initiator is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include potassium persulfate, sodium persulfate, ammonium persulfate, sodium peroxodisulfate and potassium peroxodisulfate. Be done. These may be used alone or in combination of two or more. Among these, potassium persulfate is preferable.

<< Curing process and curing means >>
The curing step is a step of irradiating a predetermined region of the hydrogel-forming material layer or the support-forming material layer formed in the curing means with active energy rays to cure the hydrogel-forming material layer.

Examples of the means for curing the layer include an ultraviolet (UV) irradiation lamp and an electron beam. Further, it is preferable that a mechanism for removing ozone is provided.
Examples of the type of the ultraviolet (UV) irradiation lamp include a high-pressure mercury lamp, an ultra-high-pressure mercury lamp, a metal halide lamp, and an ultraviolet light emitting diode (UV-LED).
The ultra-high pressure mercury lamp is a point light source, but the DeepUV type, which has high light utilization efficiency in combination with an optical system, can irradiate in a short wavelength region.
The metal halide is effective for colored substances because it has a wide wavelength region, and halides of metals such as Pb, Sn, and Fe are used and can be selected according to the absorption spectrum of the polymerization initiator. The lamp used for curing is not particularly limited and may be appropriately selected depending on the intended purpose. For example, commercially available lamps such as H lamps, D lamps, V lamps manufactured by Fusion Systems, etc. are used. Can be used.
The emission wavelength of the ultraviolet light emitting diode is not particularly limited and may be appropriately selected depending on the intended purpose. Generally, there are 365 nm, 375 nm, 385 nm, 395 nm, and 405 nm, but the wavelength of the ultraviolet light emitting diode can be selected. Considering the influence of color, short wavelength light emission is more advantageous so that the absorption of the polymerization initiator is increased. Among these, an ultraviolet light emitting diode (UV-LED) that generates less heat is used as an ultraviolet (UV) irradiation lamp because it is also used for the three-dimensional model of the present invention, which is a hydrogel that is easily affected by thermal energy. Is preferable.

The cured hydrogel material layer is preferably a hydrogel in which water and a component that dissolves in water are included in a three-dimensional network structure formed by combining a polymer and a mineral. .. The hydrogel has improved extensibility and can be peeled off integrally without breaking, which greatly simplifies the post-modeling process.

-Support (core) forming material-
The support forming material (active energy ray-curable liquid composition) is not particularly limited as long as it is a support capable of supporting the hydrogel structure of the present invention, but is formed in the hollow portion after lamination. From the viewpoint of removing the existing support, those exhibiting solubility in a solvent, those exhibiting a phase transition by heating or the like and becoming a liquid, and the like are preferable. Since the hydrogel structure of the present invention is a hydrogel, immersion in water may promote swelling of the modeled object when removing the support forming material, which is not desirable. Therefore, those showing solubility in a solvent that does not attack the hydrogel are preferable, and those having a phase change of being solid at 25 ° C. but becoming liquid at 50 ° C. are preferable. If the support forming material is a material that undergoes a phase change, it can be easily removed after the formation of the hydrogel structure.
Further, the support forming material (core forming material) for supporting the inside of the hollow shape in the hydrogel structure of the present invention and the support forming material for supporting the outside of the structure may be the same or different. Further, it is not necessary to fill the hollow inside with a support, and it is sufficient that the shape of the support is the minimum that can be supported. In this case, the removal can be performed more efficiently than the case where the hollow is filled with the support.

The support-forming material contains a polymerizable monomer, and if necessary, a polymerization initiator, a colorant, and the like, and these can be used in the same manner as the above-mentioned hydrogel-forming material.
The phase-changing material is, for example, a liquid in the state before curing, and is solidified by irradiating with active energy rays such as ultraviolet rays as in the case of hydrogel, so that the environment is at room temperature (25 ° C.). Below, those having the property of being in a solid state and being liquid in an environment of 60 ° C. can be mentioned.

In one embodiment, a monofunctional ethylenically unsaturated monomer (A) having a straight chain having 14 or more carbon atoms (hereinafter, also referred to as “monomer (A)”) and a polymerization initiator (B). , It is preferable to contain a solvent (C) capable of dissolving the monomer (A), and it is more preferable to further contain a solvent (D) in which the monomer (A) is difficult to dissolve.

<Monofunctional ethylenically unsaturated monomer (A) having a straight chain with 14 or more carbon atoms>
The monofunctional ethylenically unsaturated monomer (A) having a linear chain having 14 or more carbon atoms is not particularly limited and may be appropriately selected depending on the intended purpose. For example, acrylates such as stearyl acrylate and docosyl acrylate. Methacrylates such as stearyl methacrylate and docosyl methacrylate; acrylamides such as palmityl acrylamide and stearyl acrylamide; vinyls such as vinyl stearate and vinyl docosylate can be mentioned. These may be used alone or in combination of two or more. Among these, acrylates and acrylamide derivatives are preferable from the viewpoint of photoreactivity, and stearyl acrylates are more preferable from the viewpoint of solubility in a solvent.

Examples of the polymerization reaction of the monomer (A) include radical polymerization, ionic polymerization, coordination polymerization, ring-opening polymerization and the like. Among these, radical polymerization is preferable from the viewpoint of controlling the polymerization reaction. Therefore, the monomer (A) having a hydrogen bonding ability is preferably an ethylenically unsaturated monomer. Among these, a monofunctional ethylenically unsaturated monomer is preferable from the viewpoint of meltability.

<Polymerization initiator (B)>
The polymerization initiator (B) is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a thermal polymerization initiator and a photopolymerization initiator. Among these, a photopolymerization initiator is preferable when forming a three-dimensional object.

As the photopolymerization initiator, any substance that generates radicals by irradiation with light (particularly ultraviolet rays having a wavelength of 220 nm or more and 400 nm or less) can be used.
Examples of the photopolymerization initiator include acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p, p'-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, and Michler ketone. , Phenyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) 2-hydroxy-2-methylpropan-1-one, methylbenzoylformate, 1-hydroxycyclohexylphenylketone, azobisisobutyronitrile , Benzoyl peroxide, di-tert-butyl peroxide and the like. These may be used alone or in combination of two or more. Further, it is preferable to select a photopolymerization initiator that matches the ultraviolet wavelength of the ultraviolet irradiation device.

<Solvent (C) capable of dissolving monomer (A)>
The solvent (C) is not particularly limited as long as it is a solvent capable of dissolving the monomer (A), and can be appropriately selected depending on the intended purpose, but the crystallinity of the polymer side chain is significantly reduced. From the viewpoint of prevention, it is preferable to have a linear chain having 6 or more carbon atoms.

Examples of the solvent (C) having a straight chain having 6 or more carbon atoms include esters such as hexyl acetate and octyl acetate; alcohols such as hexanol, decanol, and dodecanol. Among these, linear alcohols are preferable in order to increase the bearing capacity of the cured product on the model material. Hydrogen bonds can be constructed by hydroxyl groups while maintaining the crystallinity of the polymer side chains. Further, a linear alcohol having one or more hydroxyl groups bonded to the primary carbon is preferable because the inhibition of crystallinity is suppressed, and 1-dodecanol is more preferable.

<Solvent (D) that is difficult to dissolve the monomer (A)>
The solvent (D) is added for the purpose of reducing the warp of the support to be shaped. It is considered that the internal stress generated during curing can be dispersed by adding a poorly soluble or insoluble solvent to the monomer.

The solvent (D) is not particularly limited as long as it is a solvent in which the monomer (A) is difficult to dissolve, and can be appropriately selected depending on the intended purpose. However, the monomer (A), the solvent (C), and the solvent (D) When mixed with, it is preferable that they are compatible with each other in an environment of 60 ° C. and exist as a liquid. Further, a polyol that can stay in the cured product without inhibiting the crystallinity of the polymer side chain and can reduce the viscosity as a support material ink is more preferable.

Examples of the polyol include polyethylene glycol (PEG), polypropylene glycol (PPG), polybutylene glycol, ethylene oxide / propylene oxide copolymer, ethylene oxide / butylene oxide copolymer, polytetramethylene ether glycol (PTMEG) and the like. Examples thereof include polyethers represented by, polycaprolactone diol (PCL), polycarbonate diol, polyesters represented by polyester polyol composed of polyol / polybasic acid, castor oil, acrylic polyol and the like. These may be used alone or in combination of two or more. Of these, polypropylene glycol is preferred.
As the copolymer, block, random, or a combination thereof can be used.

The degree of polymerization of the polyol is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 10 or more and 10,000 or less, more preferably 100 or more and 5,000 or less, and 1,000 or more and 3. 000 or less is particularly preferable. When the degree of polymerization is 10 or more, it does not volatilize even when heated and can stay in the cured product. Further, when the degree of polymerization is 10,000 or less, it can exist in a liquid at 60 ° C. without excessively increasing the viscosity.

As a criterion for dissolving the monomer (A) or making it difficult to dissolve, it is determined whether or not a monomer having a mass of 1% by mass of the solvent can be dissolved. That is, the solvent (C) can dissolve the monomer (A) having a weight of 1% by mass or more, and the solvent (D) cannot dissolve the monomer (A) having a weight of 1% by mass or more.
The method for determining the above can be carried out by adding 1% by mass of the monomer (A) to the solvent (C) or the solvent (D) and stirring for 12 hours, depending on whether or not the undissolved monomer remains.

The support forming material (active energy ray-curable liquid composition) contains 20% by mass or more and 70% by mass or less of the monofunctional ethylenically unsaturated monomer (A) having a linear chain having 14 or more carbon atoms. Is preferable, and it is more preferable that the content is 30% by mass or more and 60% by mass or less.
The active energy ray-curable liquid composition of the present invention preferably contains the polymerization initiator (B) in an amount of 0.5% by mass or more and 10% by mass or less, and more preferably 3% by mass or more and 6% by mass or less. preferable.
The active energy ray-curable liquid composition of the present invention preferably contains a solvent (C) capable of dissolving the monomer (A) in an amount of 20% by mass or more and 70% by mass or less, and preferably 30% by mass or more and 60% by mass or less. Is more preferable.

The active energy ray-curable liquid composition of the present invention preferably contains a solvent (D) that is difficult to dissolve the monomer (A) in an amount of 0% by mass or more and 40% by mass or less, and preferably contains 10% by mass or more and 30% by mass or less. Is more preferable. When the content is 0% by mass or more and 40% by mass or less, the support forming material can maintain its shape and reduce warpage. If it exceeds the above range, the support forming material tends to be deformed by the weight of the hydrogel structure or an external force applied at the time of molding.

Further, when the mass of the monomer (A) is Wa, the mass of the solvent (C) is Wc, and the mass of the solvent (D) is Wd, the relationship of 60 <[(Wc + Wd) / (Wa + Wc + Wd)] <75. When is satisfied, warpage can be suppressed while ensuring sufficient compressive stress.

In order to obtain a cured product from the liquid support forming material, for example, it is preferable to irradiate an ultraviolet exposure amount of ^{200 mJ / cm 2 or more with an ultraviolet irradiation device to cure the cured product.} As the ultraviolet irradiation device, the same device that cures the hydrogel structure can also be used.

It is preferable that the temperature and humidity of the modeling space are controlled from the start to the end of modeling. This is to prevent the modeled object from absorbing moisture or drying, and to prevent the precursor from solidifying. Specifically, it is preferable that the temperature is 25 ° C. or lower, the humidity is within the target ± 5% RH, and the humidity is 95% ± 5% RH.

In addition, it is necessary to shield the surroundings so that the ultraviolet rays emitted from the ultraviolet irradiation device are not emitted to the outside during modeling. The shielding may be a structure that shields all light, or may selectively block ultraviolet light.

When the monomer (A) contains the polymerization initiator (B) and is irradiated with ultraviolet rays to become a polymer, the solvent (C) is retained by the polymer. The polymer (A) becomes a solid by arranging carbon chains in an environment of 25 ° C. When the solvent (C) is retained in the polymer (A), it has an effect of suppressing shrinkage and warpage due to crystallization. Further, a solvent (C) having a straight chain having 6 or more carbon atoms is preferable from the viewpoint of curability.
Further, it is preferable that the solvent (C) capable of dissolving the monomer (A) is a non-reactive compound that does not react with the polymerization initiator (B).
In the present invention, the solvent (C) capable of dissolving the monomer (A) means a solvent in which the monomer (A) dissolves in the solvent (C) to form a uniform liquid.
In the present invention, the non-reactive compound refers to a compound that does not chemically react even when irradiated with ultraviolet rays.
When the solvent (C) is non-reactive, it is preferable because it does not chemically react with the photopolymerization initiator and does not inhibit the polymerization reaction of the monomer or the crystallization of the polymer side chain.

-Surface tension-
The surface tension of the support forming material in the present invention is not particularly limited and may be appropriately selected depending on the intended purpose. However, at 25 ° C., it is preferably 20 mN / m or more and 45 mN / m or less, and 25 mN / m or more and 34 mN. / M or less is more preferable. When the surface tension is 20 mN / m or more, the discharge is stable during modeling, and the discharge direction does not bend or does not discharge. When the surface tension is 45 mN / m or less, the discharge nozzle for modeling or the like When filling the liquid, it can be completely filled. The surface tension can be measured using, for example, a surface tension meter (automatic contact angle meter DM-701, manufactured by Kyowa Interface Science Co., Ltd.).

-Viscosity-
The viscosity of the support forming material in the present invention is preferably 1,000 mPa · s or less, more preferably 300 mPa · s or less, further preferably 100 mPa · s or less, and 3 mPa · s or more and 20 mPa · s or less at 25 ° C. It is particularly preferable, and 6 mPa · s or more and 12 mPa · s or less is most preferable. If the viscosity exceeds 1,000 mPa · s, the head may not be discharged even if the temperature is raised. The viscosity can be measured in an environment of 25 ° C. using, for example, a rotational viscometer (VISCOMATE VM-150III, manufactured by Toki Sangyo Co., Ltd.).

<<< Removal process and removal means >>>
The removing step is a step of removing the support including the columnar core portion.
Examples of the removal of the columnar core portion include liquefaction by heat and the use of an insoluble solvent for the tubular portion. The term "insoluble" means that, for example, when 1 g of the tubular portion is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more thereof is not dissolved.

<< Other processes and other means >>
The other steps are not particularly limited and may be appropriately selected depending on the intended purpose. For example, a layer smoothing step, a peeling step, a discharge stabilization step, a molding body cleaning step, a molding body polishing step, and the like. Can be mentioned.

(Manufacturing method of three-dimensional model and equipment for manufacturing three-dimensional model)
The method for producing a three-dimensional object of the present invention comprises producing a three-dimensional object using the active energy ray-curable liquid composition of the present invention, and further includes other steps as necessary.
Further, the method for producing a three-dimensional model of the present invention is a method of laminating layers of an active energy ray-curable liquid composition to produce a three-dimensional model, wherein the active energy ray-curable liquid composition of the present invention is produced. Laminated molding is performed so that the cured product serves as a support portion, and after the laminated molding, the support portion is removed by heating, and if necessary, other steps are included.
Further, the apparatus for producing a three-dimensional model of the present invention comprises a container containing an active energy ray-curable liquid composition, a discharge means for discharging the active energy ray-curable liquid composition, and the discharge means. It has a curing means for curing the discharged active energy ray-curable liquid composition, and further has other means as needed.

As the active energy ray-curable liquid composition, the same one as the active energy ray-curable liquid composition of the present invention (support forming material used in the layer forming step in the method for producing a hydrogel structure) may be used. can.

Further, as a method for producing the three-dimensional model, it is preferable to perform laminated modeling so that the cured product of the active energy ray-curable liquid composition serves as a support portion and the hydrogel structure of the present invention serves as a model portion.

The container containing the active energy ray-curable composition can be used as an ink cartridge or an ink bottle, so that it is not necessary to directly touch the ink in operations such as ink transfer and ink replacement, and the fingers do not need to touch the ink directly. And clothes can be prevented from getting dirty. In addition, it is possible to prevent foreign substances such as dust from being mixed into the ink. The shape, size, material, etc. of the container itself may be suitable for the intended use and usage, and is not particularly limited, but the material is a light-shielding material that does not transmit light, or the container blocks light. It is preferable that it is covered with a sex sheet or the like.

FIG. 4 is a schematic view showing an example of a modeled body manufacturing process using a three-dimensional modeling apparatus used in the method for manufacturing a hydrogel structure of the present invention.
The three-dimensional modeling apparatus 10 uses a head unit in which inkjet heads (forming material ejection means, ejection means) that can move in any of the directions of arrows A and B are arranged on the modeled object support substrate 14 from the head unit 12. The hydrogel forming material is jetted from the head unit 11 to form a support, and the hydrogel forming material is laminated while being cured by an adjacent UV irradiator (curing means) 13.
That is, the support forming material (support material) is injected from the head unit 12 and solidified to form a first support layer having a reservoir, and the hydrogel forming material is applied to the reservoir of the first support layer. The hydrogel-forming material is jetted from the head unit 11 and cured by irradiating the hydrogel-forming material with UV light, and further smoothed using the smoothing member 16 to form a first modeled object layer.

Next, a support forming material is sprayed onto the first support layer and solidified to laminate a second support layer having a reservoir, and hydrogel is formed on the reservoir of the second support layer. A material is jetted, UV light is irradiated, and a second modeled object layer is laminated on the first modeled object layer, and further smoothed to produce a modeled body 17.
When a roller-shaped smoothing member is used, the smoothing effect is more effectively exhibited by rotating the roller in the direction opposite to the operation direction.

Further, in order to keep the gap between the head unit 11, the head unit 12, and the UV irradiator 13 and the modeled body 17 and the support 18 constant, the stages 15 are laminated while being lowered according to the number of times of lamination.

Further, as the three-dimensional modeling apparatus 10, it is also possible to add a mechanism for collecting the forming material, a recycling mechanism, and the like. It may be provided with a blade for removing the forming material adhering to the nozzle surface or a detection mechanism for a non-ejection nozzle. It is also preferable to control the environmental temperature inside the device during modeling.

By using the above-mentioned device, it is possible to control the composition distribution and shape according to the condition of the treatment site of the individual patient, and to form a blood vessel model or an organ model having a patient-specific shape and physical property distribution. Can be done.

For example, using the personal data of the person to be treated (patient), it is possible to have the shape of the blood vessel of the affected part to be catheterized and to provide the hardness distribution (composition distribution) of the blood vessel as needed. In this case as well, it is created based on individual patient data.

As a method of giving the composition distribution, the amount of the solvent contained in the hydrogel can be adjusted. This can be realized by using a device having a mechanism for ejecting a plurality of compositions from each inkjet head by the method using the inkjet.

A hydrogel-forming material (hereinafter, also referred to as "Liquid A") is used as the first liquid, and the liquid is discharged from the first head. Further, as the second liquid, a solvent obtained by diluting the hydrogel forming material, mainly water and a liquid composed of a solvent soluble in water (hereinafter, also referred to as “B liquid”) is used, and the second head is used. Discharge from. Further, a support forming material used for forming a hollow tube of a blood vessel model is used as a third liquid and discharged from a third head.
A predetermined amount of the liquid A and the liquid B is printed from each inkjet head, and the amount ratio of the liquids dropped on the same location can be precisely controlled.

Hereinafter, specific embodiments of the method for producing a hydrogel structure of the present invention will be described.
A method for obtaining hydrogel structures having different hardness, compressive stress and elastic modulus will be described in more detail.
First, the surface data or solid data of the three-dimensional shape designed by the three-dimensional CAD or the three-dimensional shape captured by the three-dimensional scanner or digitizer is converted into the STL format and input to the laminated modeling apparatus.

Next, the compressive stress distribution of the three-dimensional shape is measured. The method is not particularly limited, but for example, by using MR Elastography (hereinafter, MRE), compressive stress distribution data having a three-dimensional shape is obtained, and this data is input to the laminated modeling apparatus. Based on the input compressive stress data, the mixing ratio of the liquid A and the liquid B to be discharged at the position corresponding to the three-dimensional shape data is determined.

Based on this input data, the modeling direction of the three-dimensional shape to be modeled is determined. The modeling direction is not particularly limited, but usually the direction in which the Z direction (height direction) is the lowest is selected.
After determining the modeling direction, the projected area of the three-dimensional shape on the XY plane, the XY plane, and the YY plane is obtained. The obtained block shape is sliced in the Z direction with a single layer thickness. The thickness of the layer depends on the material used, but is usually 20 μm or more and 60 μm or less. When there is only one modeled object to be modeled, this block shape is arranged so as to come to the center of the Z stage (a table on which the modeled object descends by one layer for each layer modeling). Further, when a plurality of block shapes are formed at the same time, the block shapes are arranged on the Z stage, but it is also possible to stack the block shapes. These block shaping, round slice data (slice data: contour line data), and arrangement on the Z stage can be automatically created by specifying the material to be used.

Next, the modeling process is carried out. FIG. 5 is a schematic view showing an example of a three-dimensional modeling apparatus used in the method for producing a hydrogel structure of the present invention. FIG. 6 is a schematic view showing an example of mixing the first liquid and the second liquid by the droplet ejection method. The different heads α and β (FIG. 5) are moved in both directions to discharge the liquid A and the liquid B into a predetermined region at a predetermined ratio to form dots. At that time, as shown in FIG. 6, it is possible to mix the liquid A and the liquid B at the dots to obtain a predetermined mixing ratio. Further, by forming continuous dots, a mixed liquid film of liquid A and liquid B having a predetermined mixing ratio in a predetermined region can be produced. Then, the mixed liquid film of the liquid A and the liquid B is cured by irradiating it with ultraviolet (UV) light to form a hydrogel film (layer) having a predetermined mixing ratio in a predetermined region as shown in FIG. Can be done.

After forming one layer of the hydrogel film (layer), the stage (FIG. 5) descends by the height of one layer. By forming continuous dots on the hydrogel film again, a mixed liquid film of liquid A and liquid B having a predetermined mixing ratio in a predetermined region is produced. The mixed liquid film of the liquid A and the liquid B is cured by irradiating it with ultraviolet (UV) light to form a hydrogel film. By repeating these laminations, three-dimensional modeling becomes possible.

The hydrogel structure thus three-dimensionally shaped has different mixing ratios of the liquid A and the liquid B in the hydrogel in which the liquid film of FIG. 5 is three-dimensionalized, and the elastic modulus can be continuously changed. By adjusting the compounding ratio pattern for each fault, it is possible to partially obtain a hydrogel structure having arbitrary physical characteristics.

Further, by placing an ultraviolet (UV) light irradiator adjacent to the inkjet head that injects the hydrogel forming material, the time required for the smoothing process can be saved, and high-speed modeling is possible.

The hardness of the hydrogel structure used in the present invention can be arbitrarily changed by combining a hydrogel-forming material and a diluent and changing the composition ratio while using the same material. Therefore, it is possible to easily provide the hardness distribution of blood vessels according to personal data by using a plurality of inkjet heads and changing the ratio of the two when modeling by the inkjet method.

The hydrogel has a structure containing a large amount of water and is extremely close to the composition of the human body and has a texture very close to that of the human body. Combining this with 3D printing is very useful in forming a vascular model.

Since the hydrogel structure, blood vessel model, and organ model of the present invention can be produced by 3D printing technology, it is possible to form a model that reproduces this shape and physical properties based on the affected area data of the patient. .. Therefore, it can be usefully used for simulation before difficult surgery.
For example, in conventional surgery (stent insertion into aneurysm), the shape of the aneurysm is read from an X-ray image, and a stent that seems to have an appropriate shape is selected intraoperatively and used. However, this is done based on the experience of the doctor (operator), and there were many cases where it took time to make a decision or the optimum one could not be selected.
Regarding the issue of what shape of member (stent, etc.) should be selected according to the shape and physical properties of the aneurysm, it is possible to increase the success rate of surgery by considering it before surgery. You can expect it.

The present invention also discloses another form of blood vessel model and organ model to which the technique of the present invention is applied.
The hydrogel structure of the present invention has a hollow tube structure having an inner diameter of 1.0 mm or less. In order to make this structure formable, as described above, a hollow tube structure is formed using a support forming material. As the support forming material, it is effective to use a solid material whose phase changes to a liquid by heat, but this technique can be applied.

When modeling the blood vessel model and the organ model having the hollow structure, the modeling is completed without removing the support material that fills the inside of the hollow structure. As a result, the blood vessel model and the organ model in which the phase-changing support material remains while maintaining the hollow structure are completed. The support material used here is preferably colored red to imitate blood by containing a coloring material or the like.
The blood vessel model and the organ model can be obtained by the second aspect of the method for producing a hydrogel structure of the present invention.

The blood vessel model and the organ model can be used for surgical training of surgical devices such as ultrasonic scalpels and electric scalpels. Specifically, in training for making an incision near a blood vessel placed in an organ model, it can be used as a model for bleeding when a blood vessel is accidentally damaged, which is very useful.

Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.
The inner diameter of the structure was measured as follows.

(Inner diameter of structure)
The inner diameter of the structure was measured with a one-shot 3D shape measuring instrument (manufactured by KEYENCE CORPORATION).
In order to determine the accuracy of the measurement, several samples were measured in advance, cross sections of these samples were cut out, and measurements were performed with calipers to confirm that the values were equivalent.
In the following examples, non-destructive measurement was performed with a one-shot 3D shape measuring instrument.

(Preparation Example 1 of Hydrogel Forming Material)
<Preparation of hydrogel forming material A>
While stirring 120.0 parts by mass of ion-exchanged water (hereinafter, also referred to as “pure water”) that was degassed under reduced pressure for 30 minutes, as a layered clay mineral [Mg _5.34 Li _0.66 Si ₈ O ^{_{20 (OH) 4] Na -}} 0.66 synthetic hectorite having a composition of (laponite XLG, manufactured by RockWood Ltd.) 12.0 parts by mass was added and stirred slightly. Further, 0.6 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and stirred to prepare a dispersion.
44.0 parts by mass of acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) and methylenebisacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.) from which the polymerization inhibitor was removed by passing the obtained dispersion through a column of activated alumina as a polymerizable monomer ) 0.4 parts by mass was added.
Furthermore, glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) 20.0 mass, N, N, N', N'-tetramethylethylenediamine (manufactured by Tokyo Kasei Kogyo Co., Ltd.) 0.8 parts by mass, Surflon S-243 (AGC Seimi) 0.6 parts by mass of Chemical Co., Ltd. and 1.2 parts by mass of Irgacure 184 (4% by mass methanol solution manufactured by BASF) were added and mixed to prepare a hydrogel forming material A (ink A).

(Preparation Examples 2 to 4 of Hydrogel Forming Material)
<Preparation of hydrogel forming materials B to D>
Hydrogel-forming materials B to D were prepared in the same manner as in Preparation Example 1 of the hydrogel-forming material, except that the composition was changed to the composition shown in Table 1 below in Preparation Example 1 of the hydrogel-forming material.

(Preparation Example 5 of Hydrogel Forming Material)
<Preparation of gel forming material E>
Polyvinyl alcohol having an average degree of polymerization of about 2,000 and a saponification degree of 89 mol% was dissolved in water containing 0.9% by mass of NaCl. At this time, in order to promote the dissolution of polyvinyl alcohol, it was dissolved by heating at 60 ° C. After dissolution, it was cooled to room temperature to prepare a gel-forming material E.

In Table 1, the product names of the ingredients and the names of the manufacturers are as follows.
・ Acryloyl morpholine: manufactured by KJ Chemicals Co., Ltd. ・ Methylenebisacrylamide: manufactured by Tokyo Kasei Kogyo Co., Ltd. ・ Synthetic hectorite: manufactured by RockWood, trade name: Laponite XLG
・ Glycerin: manufactured by Sakamoto Yakuhin Kogyo Co., Ltd. ・ Etidronic acid: manufactured by Tokyo Kasei Kogyo Co., Ltd. ・ N, N, N', N'-tetramethylethylenediamine: manufactured by Tokyo Kasei Kogyo Co., Ltd. S-243: manufactured by AGC Seimi Chemical Co., Ltd. ・ Irgacure184: manufactured by BASF, 4% by mass methanol solution

(Preparation Example 1 of Support (Core) Forming Material)
<Preparation of support forming material A>
1-dodecanol (manufactured by Tokyo Kasei Kogyo Co., Ltd., solvent (C)) 58.0 parts by mass, stearyl acrylate (manufactured by Tokyo Kasei Kogyo Co., Ltd., polymer (A)) 48.0 parts by mass, Irgacure 819 (manufactured by BASF, polymerization) 4.0 parts by mass of the initiator (B)) was stirred and mixed and dissolved to prepare a support forming material A. The composition is shown in Table 2 below.

(Preparation example 2 of support (core) forming material)
<Preparation of support forming material C>
1-dodecanol (manufactured by Tokyo Kasei Kogyo Co., Ltd., solvent (C)) 58.0 parts by mass, polypropylene glycol 2000 (manufactured by Tokyo Kasei Kogyo Co., Ltd., solvent (D)) 15.0 parts by mass, stearyl acrylate (Tokyo Kasei Kogyo Co., Ltd.) 48.0 parts by mass of polymer (A) manufactured by Co., Ltd. and 4.0 parts by mass of Irgacure 819 (manufactured by BASF, polymerization initiator (B)) were stirred and mixed and dissolved to prepare a support forming material C. .. The composition is shown in Table 2 below.

(Preparation Example 3 of Support (Core) Forming Material)
<Preparation of support forming material D>
1-dodecanol (manufactured by Tokyo Kasei Kogyo Co., Ltd., solvent (C)) 58.0 parts by mass, polypropylene glycol 2000 (manufactured by Tokyo Kasei Kogyo Co., Ltd., solvent (D)) 30.0 parts by mass, stearyl acrylate (Tokyo Kasei Kogyo Co., Ltd.) 48.0 parts by mass of polymer (A) manufactured by Co., Ltd. and 4.0 parts by mass of Irgacure 819 (manufactured by BASF, polymerization initiator (B)) were stirred and mixed and dissolved to prepare a support forming material D. .. The composition is shown in Table 2 below.

(Preparation Example 4 of Support (Core) Forming Material)
<Preparation of support forming material E>
1-dodecanol (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (C)) 58.0 parts by mass, polypropylene glycol 2000 (manufactured by Tokyo Chemical Industry Co., Ltd., solvent (D)) 20.0 parts by mass, stearyl acrylate (Tokyo Chemical Industry Co., Ltd.) 28.0 parts by mass of polymer (A) manufactured by Co., Ltd. and 4.0 parts by mass of Irgacure 819 (manufactured by BASF, polymerization initiator (B)) were stirred and mixed and dissolved to prepare a support forming material E. .. The composition is shown in Table 2 below.
show.

In Table 2, the product names of the ingredients and the names of the manufacturers are as follows.
・ Stearyl acrylate: manufactured by Tokyo Chemical Industry Co., Ltd. ・ 1-dodecanol: manufactured by Tokyo Chemical Industry Co., Ltd. ・ Propylene glycol 2000: manufactured by Tokyo Chemical Industry Co., Ltd. ・ Irgacure 819: manufactured by BASF

(Preparation Example 5 of Support (Core) Forming Material)
<Preparation of support forming material B>
Support forming material B was prepared by mixing and dispersing 3 parts by mass of the magenta pigment dispersion liquid prepared as follows in 100 parts by mass of the support forming material A.

<Preparation of magenta pigment dispersion>
After sufficiently replacing the inside of a 1 L flask equipped with a mechanical stirrer, a thermometer, a nitrogen gas introduction tube, a perfusion tube, and a dropping funnel with nitrogen gas, 11.2 g of styrene, 2.8 g of acrylic acid, and lauryl methacrylate 12 0.0 g, 4.0 g of polyethylene glycol methacrylate, 4.0 g of styrene macromer, and 0.4 g of mercaptoethanol were mixed and heated to 65 ° C. Next, 100.8 g of styrene, 25.2 g of acrylic acid, 108.0 g of lauryl methacrylate, 36.0 g of polyethylene glycol methacrylate, 60.0 g of hydroxylethyl methacrylate, 36.0 g of styrene macromer, 3.6 g of mercaptoethanol, and azobismethylvalero. A mixed solution of 2.4 g of nitrile and 18 g of methyl ethyl ketone was added dropwise into the flask over 2.5 hours, and then a mixed solution of 0.8 g of azobismethylvaleronitrile and 18 g of methyl ethyl ketone was added to the flask over 0.5 hours. It was dropped into the water and aged at 65 ° C. for 1 hour. Further, 0.8 g of azobismethylvaleronitrile was added and the mixture was aged for 1 hour, and then 364 g of methyl ethyl ketone was added in a flask to obtain 800 g of a 50 mass% polymer solution.

After sufficiently stirring 28 g of the polymer solution, 42 g of magenta pigment (CI Pigment Red 122), 13.6 g of a 1 mol / L potassium hydroxide aqueous solution, 20 g of methyl ethyl ketone, and 13.6 g of ion-exchanged water, a roll mill was used. It was kneaded to obtain a paste. Next, the paste was put into 200 g of pure water, and after sufficiently stirring, methyl ethyl ketone and water were distilled off using an evaporator. Further, pressure filtration was performed using a polyvinylidene fluoride membrane filter having an average pore size of 5.0 μm to obtain a magenta pigment dispersion having a pigment content of 15% by mass and a solid content of 20% by mass.

(Example 1)
Using the modeling apparatus shown in FIG. 4, a hydrogel forming material A and a support forming material A (both active energy ray-curable compositions) were discharged, and curing was repeated with ultraviolet rays to prepare a laminated model. Next, the laminated model is allowed to stand in a constant temperature bath at 50 ° C. for 30 minutes to remove it by liquefying the columnar core portion which is a cured product of the support forming material A, and further, with warm water at 50 ° C. By washing away the remaining columnar core portion, a hydrogel structure (blood vessel model) having a hollow tube structure as shown in FIG. 2 was obtained.
In the obtained hydrogel structure, the inner diameter (hollow) of the blood vessel cavity was 5 mm in the thick part and 0.4 mm in the thinnest part. The catheter was evaluated by the doctor, and the doctor was able to confirm the catheter from the outside of the blood vessel. It was also confirmed that the microcatheter reached the tip of the vascular cavity in the hydrogel structure and the hollow tube structure could be reproduced.
After the test, the hydrogel structure is cut in the longitudinal direction at the hollow tube portion to form a flat plate, and the transmittance in the wavelength range of 400 nm or more and 700 nm or less is measured by a commercially available spectrophotometer (device name: UV-3100, Co., Ltd.). It was measured by Shimadzu Corporation, using an integration unit). As a result, the transmittance was 91% or more in the wavelength range of 400 nm or more and 700 nm or less.

(Example 2)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel forming material A was changed to the hydrogel forming material B in Example 1.
The result of texture at the time of catheter insertion was equivalent to that of Example 1. The transmittance was 87% or more in the wavelength range of 400 nm or more and 700 nm or less. In addition, the inner diameter (hollow) of the blood vessel cavity in the hydrogel structure in the obtained structure was 5 mm in the thick portion and 0.3 mm in the thinnest portion.

(Example 3)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel forming material A was changed to the hydrogel forming material C in Example 1.
When the transmittance was measured in the same manner as in Example 1, the transmittance was 81% or more in the wavelength range of 400 nm or more and 700 nm or less. In addition, the inner diameter (hollow) of the blood vessel cavity in the hydrogel structure in the obtained structure was 4 mm in the thick portion and 0.2 mm in the thinnest portion.

(Example 4)
The hydrogel structure obtained in Example 1 was incorporated in a glass container as shown in FIGS. 3A and 3B. As a result of the catheter insertion evaluation by the doctor, the texture at the time of catheter insertion and the visual confirmation status of the catheter operation did not change, and the handleability was improved.

(Example 5)
The hydrogel structure obtained in Example 1 was built in a container made of polycarbonate resin. As a result of the catheter insertion evaluation by the doctor, the texture at the time of catheter insertion and the visual confirmation status of the catheter operation did not change, and the handleability was improved.

(Example 6)
A hydrogel structure was obtained in the same manner as in Example 1 except that the modeling data used for modeling was changed to the data prepared from the blood vessel CT image of the actual patient. Next, a CT image of the obtained hydrogel structure was taken and compared with a CT image of a patient's blood vessel.
As a result, it was clarified that the hollow shape of the details could be almost reproduced and the data was reproduced with an accuracy of ± 2%.

(Example 7)
In Example 1, an organ model (liver model) was formed in the same manner as in Example 1 except that the outer shape of the hydrogel forming the periphery of the hollow structure was shaped to imitate the liver as shown in FIG. Obtained.
The texture, external visibility, and transmittance data in the catheter insertion were the same as in Example 1. Since the appearance imitates an organ, it was found to be excellent in reality.

(Comparative Example 1)
Using the gel-forming material E, a cylinder having a diameter of 8 mm and a height of 50 mm was cast into a mold containing a hollow cylinder, and in order to further promote gelation, the polyvinyl was obtained by freezing and thawing 9 times. A cylinder was pulled out from the alcohol gel to obtain a gel structure having a hollow tube structure.
When the transmittance was measured in the same manner as in Example 1, the transmittance was a low value of less than 80% in the wavelength range of 400 nm or more and 700 nm or less.
The gel structure was subjected to a catheter insertion test, but due to the opacity of the gel structure, fine movement of the catheter could not be confirmed visually from the outside. The hollow tube in the obtained gel structure had an inner diameter of 8 mm.

(Comparative Example 2)
A hydrogel structure was obtained in the same manner as in Example 1 except that the hydrogel forming material B was changed to the hydrogel forming material D in Example 1.
When the transmittance was measured in the same manner as in Example 1, the transmittance was a low value of less than 80% in the wavelength range of 400 nm or more and 700 nm or less.
The obtained hydrogel structure was subjected to a catheter insertion test, but due to the opacity of the structure (transmittance is less than 80%), fine movement of the catheter could not be confirmed from the outside, and the catheter slipped. It was a bad result. The obtained hydrogel structure had an inner diameter (hollow) of 5 mm at the thick portion and 1.0 mm at the thinnest portion.

(Comparative Example 3)
A model was obtained in the same manner as in Example 1 except that the blood vessel portion was composed of SUP706 (manufactured by Stratasys), the blood vessel wall portion and the main body portion were composed of TangoBlack (manufactured by Stratasys). The obtained model was immersed in water for 12 hours to remove the support forming material to obtain a structure.
When a catheter was inserted into the obtained structure and the texture was confirmed, the blood vessels were very hard and caught, and the texture was far from the real thing. The hollow tube in the obtained hydrogel structure had an inner diameter (hollow) of 5 mm at the thick portion and 1 mm at the thinnest portion. Moreover, the transmittance of the structure was less than 80%.

Next, "visibility", "texture", and "preservability" were evaluated as follows. The results are shown in Table 3 below.

(Visibility)
Using a spectrophotometer (device name: UV-3100, manufactured by Shimadzu Corporation, using an integration unit), the transmittance in the visible light region (wavelength 400 nm or more and 700 nm or less) was measured, and based on the following evaluation criteria, " Visibility "was evaluated. When the transmittance is high, the hydrogel structure is excellent in transparency.
-Evaluation criteria-
◯: The lowest transmittance in the wavelength range of 400 nm or more and 700 nm or less is 90% or more Δ: The lowest transmittance in the wavelength range of 400 nm or more and 700 nm or less is 80% or more and less than 90% ×: The lowest transmittance in the wavelength range of 400 nm or more and 700 nm or less Low transmittance is less than 80%

(Texture)
The obtained structure was subjected to catheter insertion evaluation by a doctor, and the texture of catheter insertion (trade name: Echelon 10, manufactured by COVIDIEN) was evaluated for "texture" based on the following evaluation criteria.
-Evaluation criteria-
◯: The texture is very close to the actual blood vessel ×: The texture is far from the actual blood vessel

(Preservation)
Using the hydrogel structures prepared in Example 1, Example 4, and Example 5, the hydrogel structures were stored as they were in the atmosphere (25 ° C., 55% RH) for 3 days, and based on the following evaluation criteria. The "preservability" was evaluated.
-Evaluation criteria-
◯: Maintaining the initial state ×: The surface becomes slightly dry and the hardness increases.

(Example 8)
In Example 1, a hydrogel structure (blood vessel model) was prepared by using the support forming material B instead of the support forming material A. The produced laminated model was cleaned by wiping the periphery with ethanol-impregnated cotton at room temperature (25 ° C) so that the support forming material B contained in the hollow structure did not flow out, and the modeling was completed. ..
The produced laminated model was tested with an electric knife (general electrosurgical instrument, Prog DS3-M, manufactured by Morita Tokyo Seisakusho Co., Ltd.). When the blood vessel site was incised, the support forming material B melted and flowed out as pseudo blood.

(Example 9)
A hydrogel structure (blood vessel model) having a hollow tube structure was obtained in the same manner as in Example 5 except that the support forming material A was changed to the support forming material C in Example 5.
With respect to the obtained hydrogel structure, the inner diameter of the structure, the result of catheter insertion, and the transmittance were evaluated in the same manner as in Example 1. The inner diameter of the structure, the result of catheter insertion, and the result of transmittance were the same as in Example 5.

(Example 10)
A hydrogel structure (blood vessel model) having a hollow tube structure was obtained in the same manner as in Example 5 except that the support forming material A was changed to the support forming material D in Example 5.
With respect to the obtained hydrogel structure, the inner diameter of the structure, the result of catheter insertion, and the transmittance were evaluated in the same manner as in Example 1. The inner diameter of the structure, the result of catheter insertion, and the result of transmittance were the same as in Example 5.

(Example 11) A hydrogel structure (blood vessel model) having a hollow tube structure is used in the same manner as in Example 5 except that the support forming material A is changed to the support forming material E in Example 5. Obtained.
With respect to the obtained hydrogel structure, the inner diameter of the structure, the result of catheter insertion, and the transmittance were evaluated in the same manner as in Example 1. The inner diameter of the structure, the result of catheter insertion, and the result of transmittance were the same as in Example 5.

Next, the "warp of the support" was evaluated as follows. The results are shown in Table 4 below.

(Curly of support)
During the modeling of the hydrogel structure, stop the modeling machine when half of the entire structure is completed, observe the state of the hydrogel and the support, and perform "warp of the support" based on the following evaluation criteria. evaluated. In Example 5, the warp of the support was evaluated in the same manner as in Examples 9 to 11. In addition, in the state of ×, modeling cannot be continued-evaluation criteria-
◯: Hydrogel and support are integrated Δ: The circumference of the support is slightly warped ×: The support is greatly warped and interferes with the inkjet head.

In Example 5, when the modeled object that was modeled and completed in the state of Δ was confirmed, the disorder of the modeling was confirmed at the end portion and the upper part of the hollow pipe.

In Examples 9 to 11, by adding the solvent (D) in which the monomer (A) is difficult to dissolve into the support forming material, the warp of the supported support to be formed is reduced, and an accurate modeled product is obtained. be able to.

(Preparation Example 6 of Hydrogel Forming Material)
<Preparation of the first liquid A1>
While stirring 51.0 parts by mass of ion-exchanged water (hereinafter, also referred to as “pure water”) that has been degassed under reduced pressure for 30 minutes, as a layered clay mineral [Mg _5.34 Li _0.66 Si ₈ O ^{_{20 (OH) 4] Na -}} 0.66 synthetic hectorite having a composition of (laponite XLG, manufactured by RockWood Ltd.) 5.5 parts by weight was added and stirred slightly. Further, 0.3 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and stirred at 40 ° C. for 2 hours to prepare a dispersion.
16.8 parts by mass of acryloylmorpholin (manufactured by KJ Chemicals Co., Ltd.) and methylenebisacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.) from which the polymerization inhibitor was removed by passing the obtained dispersion through a column of active alumina as a polymerizable monomer. ) 0.2 parts by mass and 3.0 parts by mass of N, N-dimethylacrylamide (manufactured by KJ Chemicals Co., Ltd.) were added.
Further, 22.0 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) and 0.3 parts by mass of Emargen LS106 (manufactured by Kao Corporation) were added. Next, after shading the container, 0.5 parts by mass of Irgacure 1173 (manufactured by BYK) and 0.4 parts by mass of N, N, N', N'-tetramethylethylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) were added. Then, the mixture was stirred and mixed for 30 minutes. Next, after degassing under reduced pressure for 10 minutes, filtration was performed using a syringe filter (manufactured by ADVANTEC) having an average pore size of 0.8 μm to obtain a homogeneous first liquid A1.

(Preparation Example 1 of Diluting Material)
<Preparation of the second liquid B1>
A second liquid B1 was prepared in the same manner as in Preparation Example 6 of the hydrogel-forming material, except that the composition was changed to the composition shown in Table 5 below in Preparation Example 6 of the hydrogel-forming material.

In Table 5, the product names of the ingredients and the names of the manufacturers are as follows.
・ Acryloyl morpholine: manufactured by KJ Chemicals Co., Ltd. ・ Methylenebisacrylamide: manufactured by Tokyo Kasei Kogyo Co., Ltd. ・ N, N-dimethylacrylamide: manufactured by KJ Chemicals Co., Ltd., monofunctional monomer ・ Synthetic hectorite: manufactured by RockWood, trade name: Laponite XLG
・ Glycerin: manufactured by Sakamoto Yakuhin Kogyo Co., Ltd. ・ Etidronic acid: manufactured by Tokyo Kasei Kogyo Co., Ltd. ・ N, N, N', N'-tetramethylethylenediamine: manufactured by Tokyo Kasei Kogyo Co., Ltd. : Made by BYK

(Preparation Example 6 of Support (Core) Forming Material)
<Preparation of support forming material 1>
1-Dodecanol (manufactured by Tokyo Kasei Kogyo Co., Ltd.) 55.0 parts by mass, stearyl acrylate (manufactured by Tokyo Kasei Kogyo Co., Ltd.) 42.0 parts by mass, and Irgacure 819 (manufactured by BASF) 3.0% by mass at 40 ° C. The temperature was adjusted, the mixture was stirred for 30 minutes, and the mixture was mixed and dissolved to prepare a support forming material 1. The composition is shown in Table 6 below.

In Table 6 above, the product names of the ingredients and the names of the manufacturers are as follows.
・ Stearyl acrylate: manufactured by Tokyo Chemical Industry Co., Ltd. ・ 1-dodecanol: manufactured by Tokyo Chemical Industry Co., Ltd. ・ Irgacure 819: manufactured by BASF

(Reference Examples 1-2)
The first liquid A1 and the second liquid B1 are mixed in the volume ratio shown in Table 7 below and poured into a mold of 30 mm × 30 mm × 8 mm, and an ultraviolet irradiator (device name: SPOT CURE SP5-250DB, Ushio, Inc.) After curing with (manufactured by the company), the mixture was allowed to stand at 27 ° C. for 12 hours to obtain a hydrogel sample for a compression test of Reference Examples 1 and 2. The water content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 7 below.

(Moisture content)
The moisture content was measured using a heat-drying moisture meter (device name: MS-70, manufactured by A & D Co., Ltd.).

(Elastic modulus)
For the elastic modulus, a universal testing machine (device name: AG-I, manufactured by Shimadzu Corporation), a compression jig for load cells 1 kN and 1 kN were provided, and a sample shaped into a shape of 30 mm × 30 mm × 8 mm was installed. The stress on the compression applied to the load cell was recorded on a computer, and the stress on the displacement was plotted. The elastic modulus indicates the slope of the compressive stress at the time of 20% compression.

(Examples 12 to 13)
Using the modeling apparatus shown in FIG. 4, the first liquid A1 and the second liquid B1 and the support forming material 1 (both are active energy ray-curable compositions) are discharged at the volume ratio shown in Table 8 below. , Curing with ultraviolet rays was repeated to prepare a laminated model. Next, the laminated model is allowed to stand in a constant temperature bath at 50 ° C. for 30 minutes to remove the support (columnar core) which is a cured product of the support forming material 1, and further, 50. By washing away the remaining support (columnar core portion) with warm water at ° C., a hydrogel structure having a hollow tube shape as shown in FIG. 1 was obtained. In each of the obtained hydrogel structures, the blood vessel wall had a harder composition than the other surrounding hydrogels. As a result of inserting a catheter into this and checking the texture, the texture was very close to that of an actual blood vessel. The water content and elastic modulus are the same as those in Reference Example 1.

(Comparative Examples 4 to 5)
In Example 12, a hydrogel structure was obtained in the same manner as in Example 12 except that the volume ratio was changed as shown in Table 8 below. When a catheter was inserted into the obtained hydrogel structure and the texture was confirmed, the texture was different from the actual one. The elastic modulus was measured in the same manner as in Reference Example 1. The results were 0.21 MPa for the blood vessel wall in Comparative Example 4, 0.21 MPa for the other hydrogel, 0.02 MPa for the blood vessel wall in Comparative Example 5, and 0.02 MPa for the other hydrogel.

(Comparative Example 6)
A modeled object was obtained in the same manner as in Example 12 except that the support (columnar core) was made of SUP706 (manufactured by Stratasys) and the blood vessel wall and the main body were made of TangoBlack (manufactured by Stratasys). .. The obtained model was immersed in water for 12 hours to remove the support forming material to obtain a structure.
When a catheter was inserted into the obtained structure and the texture was confirmed, the blood vessels were very hard and caught, and the texture was far from the real thing. The elastic modulus was measured in the same manner as in Reference Example 1. The result was 2.0 MPa for both the vessel wall and the other hydrogels.

Next, the "texture" was evaluated as follows. The results are shown in Table 8 below.

(Texture)
The obtained hydrogel structure was subjected to catheter insertion evaluation by a doctor, and the texture of catheter insertion (trade name: Echelon 10, manufactured by COVIDIEN) was evaluated for "texture" based on the following evaluation criteria.
-Evaluation criteria-
◯: The texture is very close to that of an actual blood vessel and is a level that can be preferably used for catheter insertion practice. △: The texture is different from that of an actual blood vessel, but it is a level that can be used for catheter insertion practice. Is a texture far from that, and it is a level that can not be used for catheter insertion practice

(Example 14)
The hydrogel structure obtained in the same manner as in Example 12 was incorporated in a glass container. The texture when inserting the catheter did not change, and the handleability was improved.

(Example 15)
The hydrogel structure obtained in the same manner as in Example 12 was incorporated in a container made of polycarbonate resin. The texture when inserting the catheter did not change, and the handleability was improved.

Next, the "preservability" was evaluated as follows.

(Preservation)
Using the hydrogel structures prepared in Example 12, Example 14, and Example 15, the hydrogel structures were stored as they were in the air (25 ° C., 55% RH) for 3 days.
As a result, the surface of the hydrogel structure of Example 12 was slightly dried and the hardness was increased, but no change was observed in the structures of Examples 14 and 15.

(Preparation Example 7 of Hydrogel Forming Material)
<Preparation of the first liquid A2>
Hereinafter, the ion-exchanged water that has been degassed under reduced pressure for 30 minutes is referred to as pure water.
First, while stirring the pure water 60.0 parts by _{weight, [Mg 5.34 Li 0.66 Si 8} O 20 (OH) 4] Na as layered clay mineral _- synthetic hectorite (trade having a composition of _0.66 Name: Laponite XLG, manufactured by RockWood Co., Ltd.) was added little by little so as to have a total of 6.0 parts by mass, and the mixture was stirred to prepare a dispersion. Next, 0.3 parts by mass of etidronic acid was added as a dispersant for synthetic hectorite.
Next, the obtained dispersion was passed through a column of activated alumina as a polymerizable monomer to remove the polymerization inhibitor, and 22.0 parts by mass of acryloylmorpholin (manufactured by KJ Chemicals Co., Ltd.), methylenebisacrylamide (organic cross-linking agent). , Tokyo Kasei Kogyo Co., Ltd.) 0.2 parts by mass, glycerin 10.2 parts by mass as a drying inhibitor, and Emargen LS106 (manufactured by Kao Co., Ltd.) 0.3 parts by mass were added and mixed.
Next, 0.4 parts by mass of N, N, N', N'-tetramethylethylenediamine was added as a polymerization accelerator, and then 0.6 parts by mass of Irgacure184 (manufactured by BASF) was added as a polymerization initiator and mixed by stirring. bottom.
After stirring and mixing, degassing under reduced pressure was carried out for 10 minutes. Subsequently, by performing filtration, impurities and the like were removed to obtain a homogeneous first liquid A2. The composition is shown in Table 9 below.

(Preparation Example 2 of Diluted Material)
<Preparation of the second liquid B2>
A second liquid B2 was obtained in the same manner as in Preparation Example 7 of the hydrogel-forming material, except that the composition was changed to the composition shown in Table 9 below in Preparation Example 7 of the hydrogel-forming material.

In Table 9, the product names of the ingredients and the names of the manufacturers are as follows.
・ Acryloyl morpholine: manufactured by KJ Chemicals Co., Ltd. ・ Methylenebisacrylamide: manufactured by Tokyo Kasei Kogyo Co., Ltd. ・ Synthetic hectorite :: manufactured by RockWood, trade name: Laponite XLG
・ Glycerin: manufactured by Sakamoto Pharmaceutical Industry Co., Ltd. ・ Etidronic acid: manufactured by Tokyo Chemical Industry Co., Ltd. ・ N, N, N', N'-tetramethylethylenediamine: manufactured by Tokyo Chemical Industry Co., Ltd. : Made by BASF

(Reference Examples 3 to 5)
As the hydrogel forming material, the first liquid A2 and the second liquid B2 are mixed at the volume ratio shown in Table 10 below and poured into a mold of 30 mm × 30 mm × 8 mm, and an ultraviolet irradiator (device name: SPOT CURE SP5). After curing with −250DB (manufactured by Ushio Denki Co., Ltd.), the mixture was allowed to stand at 27 ° C. for 12 hours to obtain a hydrogel sample for a compression test of Reference Examples 3 to 5. The water content and elastic modulus of the obtained hydrogel sample were measured. The results are shown in Table 10 below.

From the results in Table 10 above, it was found that in Reference Examples 3 to 5, predetermined strength (compressive stress, elastic modulus) and water content can be set by adjusting the volume ratio of the first liquid and the second liquid. ..

(Preparation Example 7 of Support (Core) Forming Material)
<Preparation of support forming material 2>
1-Dodecanol (manufactured by Tokyo Kasei Kogyo Co., Ltd.) 50.0 parts by mass, acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) 46.0 parts by mass, and Irgacure 819 (manufactured by BASF) 4.0 parts by mass are stirred and mixed and dissolved. The support forming material 2 was prepared. The composition is shown in Table 11 below.

(Example 16)
Using the modeling apparatus shown in FIG. 4, the first liquid A2, the second liquid B2, and the support forming material 2 (both are active energy ray-curable compositions) are discharged at the volume ratio shown in Table 12 below. , Curing with ultraviolet rays was repeated to prepare a laminated model. Next, the laminated model is allowed to stand in a constant temperature bath at 50 ° C. for 30 minutes to remove the support (columnar core) which is a cured product of the support forming material 2, and further, 50. By washing away the remaining support (columnar core portion) with warm water at ° C., a hydrogel structure having a hollow tube shape as shown in FIG. 2B was obtained. The elastic modulus, the maximum inner diameter of the thinnest part, and the transmittance were measured in the same manner as in Example 1. The results are shown in Tables 12 and 13 below.

(Example 17)
In Example 16, a structure having a bump portion as shown in FIG. 2B was obtained in the same manner as in Example 16 except that the volume ratio was changed to that shown in Table 12 below. The elastic modulus, the maximum inner diameter of the thinnest part, and the transmittance were measured in the same manner as in Example 1. The results are shown in Tables 12 and 13 below.

(Comparative Examples 7 to 8)
In Example 16, a hydrogel structure was obtained in the same manner as in Example 16 except that the volume ratios were changed to those shown in Table 12 below. The elastic modulus, the maximum inner diameter of the thinnest part, and the transmittance were measured in the same manner as in Example 1. The results are shown in Tables 12 and 13 below.

(Comparative Example 9)
The same as in Example 16 except that the support (columnar core) was made of SUP706 (manufactured by Stratasys) and the other hydrogel, blood vessel wall, and aneurysm were made of TangoBlack (manufactured by Stratasys). , I got a model. The obtained model was immersed in water for 12 hours to remove the support forming material to obtain a structure. The elastic modulus was measured in the same manner as in Reference Example 1. The results were 2.0 MPa, respectively.

Moreover, the "texture" was evaluated in the same manner as in Example 1. The results are shown in Table 13 below.

In Example 16, the aneurysm portion was able to reproduce a texture close to that of an actual aneurysm portion, and was able to reproduce a texture very close to that of an actual blood vessel.
In Example 17, the blood vessel wall portion had the same hardness as the peripheral portion, but the texture of the same hardness as that of the mouse having a low blood vessel wall hardness could be reproduced.
In Comparative Examples 7 to 9, the blood vessels were very hard, caught, and had a texture far from the real thing.

From the above results, as in the examples, the vascular model composed of the hydrogel structure and partially adjusted in hardness and water content has a texture very close to the real thing, preoperative simulation and vascular catheter insertion. It became clear that it was suitable for practice.

Examples of aspects of the present invention are as follows.
<1> A hydrogel structure having a hollow tube structure having an inner diameter of 1.0 mm or less and having a transmittance of 80% or more in the visible light region.
<2> The hydrogel structure according to <1>, wherein the inner diameter is 0.3 mm or less.
<3> The hydrogel structure according to any one of <1> to <2>, wherein the transmittance in the visible light region is 90% or more.
<4> The hydrogel structure according to any one of <1> to <3>, wherein a solid material whose phase changes to a liquid by heat exists in the hollow of the hollow tube structure.
<5> The hydrogel structure according to <4>, which contains a coloring material in the hollow of the hollow tube structure.
<6> (1) At least a part of the hollow tube structure is in contact with a second hydrogel body having an elastic modulus different from that of the first hydrogel body constituting the hollow tube structure, or (2) the above. The hydrogel structure according to any one of <1> to <5>, wherein the hollow tube structure is formed of at least two types of hydrogel bodies having different elastic moduli.
<7> The water content of the first hydrogel body having the hollow tube structure is lower than the water content of the second hydrogel body having an elastic coefficient different from that of the first hydrogel body. > Is the hydrogel structure.
<8> The elastic modulus of the first hydrogel body having the hollow tube structure is 0.1 MPa or more and 0.5 MPa or less.
The hydro according to any one of <6> to <7>, wherein the elastic modulus of the second hydrogel body having an elastic modulus different from that of the first hydrogel body is 0.005 MPa or more and 0.1 MPa or less. It is a gel structure.
<9> When the elastic modulus of one part of the hollow tube structure is X (MPa) and the elastic modulus of another part adjacent to the one part is Y (MPa), the absolute value of the change in elastic modulus. The hydrogel structure according to any one of <1> to <8>, wherein (| XY |) is 0.1 MPa or more.
<10> The arithmetic mean surface roughness of at least a part of the inner walls of the hollow tube structure is 50 μm or less, or the coefficient of static friction of at least a part of the inner walls of the hollow tube structure is 0.1 or less. The hydrogel structure according to any one of <1> to <9>.
<11> A blood vessel model characterized by comprising the hydrogel structure according to any one of <1> to <10>.
<12> An organ model comprising the hydrogel structure according to any one of <1> to <11>, wherein the outer shape thereof imitates the shape of an organ.
<13> At least one of the blood vessel model according to <11> and the organ model according to <12>.
A procedure training tool characterized by having at least one of a catheter and an endoscope.
<14> A method for producing a hydrogel structure having a hollow tube structure.
Hydro is characterized in that a columnar core portion is formed using a core portion forming material, and the columnar core portion is coated with a hydrogel forming material to form a tubular portion, and the columnar core portion is removed. This is a method for producing a gel structure.
<15> The method for producing a hydrogel structure according to <14>, wherein the columnar core portion and the tubular portion are formed by a layered manufacturing method.
<16> The method for producing a hydrogel structure according to any one of <14> to <15>, wherein both the core forming material and the hydrogel forming material are active energy ray-curable compositions.
<17> The method for producing a hydrogel structure according to any one of <14> to <16>, wherein the columnar core portion is removed by liquefaction by heat.
<18> A method for producing a hydrogel structure having a hollow tube structure.
A step of forming a columnar core portion using a core portion forming material and coating the columnar core portion with a hydrogel forming material to form a tubular portion is included.
A method for producing a hydrogel structure, wherein the core forming material is an active energy ray-curable composition, and the cured product of the active energy ray-curable composition is a material that is liquefied by heat. be.
<19> A solvent (C) capable of dissolving a monofunctional ethylenically unsaturated monomer (A) having a linear chain having 14 or more carbon atoms, a polymerization initiator (B), and the monofunctional ethylenically unsaturated monomer (A). And, including
It is an active energy ray-curable liquid composition characterized in that the cured product is a solid in an environment of 25 ° C. and a liquid in an environment of 60 ° C.
<20> The active energy ray-curable liquid composition according to <19>, which further contains a solvent (D) that is difficult to dissolve the monofunctional ethylenically unsaturated monomer (A).
<21> A method for producing a three-dimensional model, which comprises producing the three-dimensional model using the active energy ray-curable liquid composition according to any one of <19> to <20>.
<22> A method of laminating layers of an active energy ray-curable liquid composition to produce a three-dimensional model.
Laminate molding is performed so that the cured product of the active energy ray-curable liquid composition according to any one of <19> to <20> serves as a support portion, and after the laminate molding, the support portion is removed by heating. This is a method for manufacturing a three-dimensional model, which is characterized by the above.
<23> The cured product of the active energy ray-curable liquid composition according to any one of <19> to <20> serves as a support unit.
The method for producing a three-dimensional model according to any one of <21> to <22>, wherein the hydrogel structure according to any one of <1> to <10> is laminated and shaped so as to be a model portion. ..
<24> A container containing the active energy ray-curable liquid composition according to any one of <19> to <20>.
Discharging means for discharging the active energy ray-curable liquid composition and
An apparatus for producing a three-dimensional model, which comprises a curing means for curing the active energy ray-curable liquid composition discharged by the discharging means.

The hydrogel structure according to any one of <1> to <10>, the blood vessel model according to <11>, the organ model according to <12>, and the procedure practice tool according to <13>. From the method for producing a hydrogel structure according to any one of <14> to <18>, the active energy ray-curable composition according to any one of <19> to <20>, and the above <21>. According to the method for producing a three-dimensional model according to any one of <24>, the conventional problems can be solved and the object of the present invention can be achieved.

10 Three-dimensional modeling device 11, 12 Head unit 13 UV irradiator 14 Modeled object support substrate 15 Stage 16 Smoothing member 17 Modeled body 18 Support (support material)

Japanese Unexamined Patent Publication No. 2015-69054 Japanese Unexamined Patent Publication No. 2015-219371 Japanese Unexamined Patent Publication No. 2012-189909 JP-A-2009-273508 Japanese Patent No. 4993519 Japanese Patent No. 5745155

Claims (10)

It has a hollow tube structure with an inner diameter of 1.0 mm or less, and has an inner diameter of 1.0 mm or less.
The transmittance in the visible light region is 80% or more, and
A hydrogel structure characterized in that a solid material whose phase changes to a liquid by heat exists in the hollow of the hollow tube structure. The hydrogel structure according to claim 1, wherein the inner diameter is 0.3 mm or less. The hydrogel structure according to any one of claims 1 to 2, wherein the transmittance in the visible light region is 90% or more. The hydrogel structure according to any one of claims 1 to 3, wherein a coloring material is contained in the hollow of the hollow tube structure. (1) At least a part of the hollow tube structure is in contact with or is in contact with a second hydrogel body having an elastic modulus different from that of the first hydrogel body constituting the hollow tube structure.
(2) The hydrogel structure according to any one of claims 1 to 4, wherein the hollow tube structure is formed of at least two types of hydrogels having different elastic moduli. From claim 1, the arithmetic mean surface roughness of at least a part of the inner wall of the hollow tube structure is 50 μm or less, or the coefficient of static friction of at least a part of the inner wall of the hollow tube structure is 0.1 or less. 5. The hydrogel structure according to any one of 5. A blood vessel model comprising the hydrogel structure according to any one of claims 1 to 6. An organ model comprising the hydrogel structure according to any one of claims 1 to 6, wherein the outer shape thereof imitates the shape of an organ. At least one of the blood vessel model according to claim 7 and the organ model according to claim 8.
A procedure training tool characterized by having at least one of a catheter and an endoscope. A method for producing a hydrogel structure having a hollow tube structure.
A step of forming a columnar core portion using a core portion forming material and coating the columnar core portion with a hydrogel forming material to form a tubular portion is included.
A method for producing a hydrogel structure, wherein the core forming material is an active energy ray-curable composition, and the cured product of the active energy ray-curable composition is a material that is liquefied by heat.

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